Big Data Approaches to Phenotyping Acute Ischemic Stroke Using Automated Lesion Segmentation of Multi-Center Magnetic Resonance Imaging Data

Author:

Wu Ona1,Winzeck Stefan12,Giese Anne-Katrin3,Hancock Brandon L.1,Etherton Mark R.3,Bouts Mark J.R.J.1,Donahue Kathleen3,Schirmer Markus D.3,Irie Robert E.1,Mocking Steven J.T.1,McIntosh Elissa C.1,Bezerra Raquel1,Kamnitsas Konstantinos4,Frid Petrea5,Wasselius Johan56,Cole John W.7,Xu Huichun8,Holmegaard Lukas9,Jiménez-Conde Jordi10,Lemmens Robin111213,Lorentzen Eric14,McArdle Patrick F.8,Meschia James F.15,Roquer Jaume10,Rundek Tatjana16,Sacco Ralph L.16,Schmidt Reinhold17,Sharma Pankaj1819,Slowik Agnieszka20,Stanne Tara M.14,Thijs Vincent2122,Vagal Achala23,Woo Daniel24,Bevan Stephen25,Kittner Steven J.7,Mitchell Braxton D.826,Rosand Jonathan27,Worrall Bradford B.28,Jern Christina14,Lindgren Arne G.529,Maguire Jane30,Rost Natalia S.3,

Affiliation:

1. From Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown (O.W., S.W., B.L.H., M.J.R.J.B., R.E.I., S.J.T.M., E.C.M., R.B.)

2. Division of Anaesthesia, Department of Medicine, University of Cambridge, United Kingdom (S.W.)

3. Department of Neurology, JP Kistler Stroke Research Center, MGH, Boston, MA (A.-K.G., M.R.E., K.D., M.D.S., N.S.R.)

4. Department of Computing, Imperial College London, United Kingdom (K.K.)

5. Department of Clinical Sciences Lund, Lund University, Sweden (P.F., J.W., A.G.L.)

6. Department of Radiology (J.W.), Skåne University Hospital, Lund, Sweden

7. Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore, MD (J.W.C., S.J.K.)

8. Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD (H.X., P.F.M., B.D.M.)

9. Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Sweden (L.H.)

10. Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d’Investigacions Mèdiques), Universitat Autonoma de Barcelona, Spain (J.J.-C., J.R.)

11. Department of Neurosciences, Experimental Neurology, KU Leuven—University of Leuven (R.L.)

12. VIB—Center for Brain & Disease Research (R.L.)

13. Department of Neurology, University Hospitals Leuven, Belgium (R.L.)

14. Department of Laboratory Medicine, Institute of Biomedicine, the Sahlgrenska Academy at University of Gothenburg, Sweden (E.L., T.M.S., C.J.)

15. Department of Neurology, Mayo Clinic, Jacksonville, FL (J.F.M.)

16. Department of Neurology, Miller School of Medicine, University of Miami, The Evelyn F. McKnight Brain Institute, FL (T.R., R.L.S.)

17. Clinical Division of Neurogeriatrics, Department of Neurology, Medical University Graz, Austria (R.S.)

18. Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, United Kingdom (P.S.)

19. Ashford and St Peter’s Hospital, United Kingdom (P.S.)

20. Department of Neurology, Jagiellonian University Medical College, Krakow, Poland (A.S.)

21. Stroke Division, Florey Institute of Neuroscience and Mental Health, HDB, Australia (V.T.)

22. Department of Neurology, Austin Health, HDB, Australia (V.T.)

23. Department of Radiology (A.V.), University of Cincinnati College of Medicine, OH

24. Department of Neurology and Rehabilitation Medicine (D.W.), University of Cincinnati College of Medicine, OH

25. School of Life Science, University of Lincoln, United Kingdom (S.B.)

26. Geriatrics Research and Education Clinical Center, Baltimore Veterans Administration Medical Center, MD (B.D.M.)

27. Henry and Allison McCance Center for Brain Health Massachusetts General Hospital, Boston (J.R.)

28. Departments of Neurology and Public Health Sciences, University of Virginia, Charlottesville (B.B.W.)

29. Department of Neurology and Rehabilitation Medicine, Neurology (A.G.L.), Skåne University Hospital, Lund, Sweden

30. University of Technology Sydney, Australia (J.M.).

Abstract

Background and Purpose— We evaluated deep learning algorithms’ segmentation of acute ischemic lesions on heterogeneous multi-center clinical diffusion-weighted magnetic resonance imaging (MRI) data sets and explored the potential role of this tool for phenotyping acute ischemic stroke. Methods— Ischemic stroke data sets from the MRI-GENIE (MRI-Genetics Interface Exploration) repository consisting of 12 international genetic research centers were retrospectively analyzed using an automated deep learning segmentation algorithm consisting of an ensemble of 3-dimensional convolutional neural networks. Three ensembles were trained using data from the following: (1) 267 patients from an independent single-center cohort, (2) 267 patients from MRI-GENIE, and (3) mixture of (1) and (2). The algorithms’ performances were compared against manual outlines from a separate 383 patient subset from MRI-GENIE. Univariable and multivariable logistic regression with respect to demographics, stroke subtypes, and vascular risk factors were performed to identify phenotypes associated with large acute diffusion-weighted MRI volumes and greater stroke severity in 2770 MRI-GENIE patients. Stroke topography was investigated. Results— The ensemble consisting of a mixture of MRI-GENIE and single-center convolutional neural networks performed best. Subset analysis comparing automated and manual lesion volumes in 383 patients found excellent correlation (ρ=0.92; P <0.0001). Median (interquartile range) diffusion-weighted MRI lesion volumes from 2770 patients were 3.7 cm 3 (0.9–16.6 cm 3 ). Patients with small artery occlusion stroke subtype had smaller lesion volumes ( P <0.0001) and different topography compared with other stroke subtypes. Conclusions— Automated accurate clinical diffusion-weighted MRI lesion segmentation using deep learning algorithms trained with multi-center and diverse data is feasible. Both lesion volume and topography can provide insight into stroke subtypes with sufficient sample size from big heterogeneous multi-center clinical imaging phenotype data sets.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)

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